We present the first documented case of a 69 year-old female with history of sickle cell anemia with hereditary persistence of fetal hemoglobin that presented due to joint pains and COVID-19 infection. The red blood cell exchange transfusion may play an important factor in preventing intubations and longer hospital stays.

SARS-CoV-2 non-structural protein 1 (Nsp1) is a virulence factor that inhibits the innate immune response and translation of host mRNAs. Despite the relevance of Nsp1, few studies have been conducted to understand the effect of mutations on Nsp1 structure and function. Here, we provide a molecular dynamics simulation of SARS-CoV-2 and SARS-CoV-1 Nsp1 conformational changes. Our data supports the idea that SARS-CoV-2 Nsp1 has a less compact structure than SARS-CoV-1 Nsp1. Moreover, several mutations in the helix-loop-helix motif of Nsp1 C-terminal that may affect the interactions of the Nsp1-ribosome complex were investigated. Disordered regions in Nsp1 probably affect host-virus interactions, cross-species transmission, and virus-host range. Overall, these findings reinforce the importance of studying Nsp1 conformational changes in new variants and its effect on virulence of SARS-CoV-2, by altering inhibition potency of host mRNA translation efficiency.

The COVID-19 pandemic has raised concern of viral transmission during otolaryngological procedures by means of droplets/saliva. The use of PPE and isolation settings are mandatory during surgery. This paper describes the development of the STAPID setting to reduce salivary spread during a sialendoscopy-assisted transfacial removal of a parotid stone.

1. Environmental soundscapes are increasingly being used as descriptors of ecosystem health and vocal animal biodiversity. Soundscape data can quickly become very expensive and difficult to manage, so data compression or temporal down-sampling are sometimes employed to reduce data storage and transmission costs. These parameters vary widely between experiments, with the consequences of this variation remaining mostly unknown. 2. We analyse field recordings from North-Eastern Borneo across a gradient of historical land-use. We quantify the impact of experimental parameters (mp3 compression, recording length and temporal subsetting) on soundscape descriptors (Analytical Indices and a convolutional neural net derived AudioSet Fingerprint). Both descriptor types were tested for their robustness to parameter alteration and their usability in a landscape classification task. 3. We find that compression and frame size both drive considerable variation in calculated index values. However, we find that the effects of this varaiation and temporal subsetting on the performance of classification models is minor: performance is much more strongly determined by acoustic index choice, with Audioset fingerprinting offering substantial (12-16%) increases in all of classifier accuracy, precision and recall. 4. We advise using the AudioSet Fingerprint in soundscape analysis, demonstrating its superior and consistent performance even on small pools of data. If data storage is a bottleneck to a study, we recommend Variable Bit Rate encoded compression (quality=0, 23% file size) to reduce file size without affecting most Analytical Index values. The AudioSet Fingerprint can be confidently compressed further to a Constant Bit Rate encoding of 64kb/s (8% file size) without any detectable effect. These recommendations balance the efficient use of restricted data storage against the comparability of results between different studies.

Background and Purpose: The insular cortex (IC) is a brain structure involved in the modulation of autonomic, cardiovascular and neuroendocrine adjustments during stress situations. However, the local neurochemical mechanisms involved in the control of these responses by the IC are poorly understood. Glutamate is a prominent excitatory neurotransmitter in the brain. Thus, the current study aimed to investigate the involvement of glutamatergic neurotransmission within the IC in cardiovascular, autonomic and neuroendocrine responses to acute restraint stress. Experimental Approach: The selective NMDA glutamate receptor antagonist LY235959 (1 nmol/100 nL) and the selective non-NMDA glutamate receptor antagonist NBQX (1 nmol/100 nL) were microinjected into the IC 10 min before the onset of restraint stress. Key Results: The antagonism of NMDA receptors within the IC potentiated the restraint-evoked increases in both arterial pressure and heart rate, while non-NMDA blockade had no effect on these parameters. Spontaneous baroreflex analysis demonstrated that microinjection of LY235959 into the IC decreased baroreflex activity during restraint stress. The decrease in tail skin temperature during restraint stress was shifted to an increase in animals treated with the NMDA receptor antagonist. Moreover, the blockade of IC glutamate receptors did not affect the increase in circulating corticosterone levels during restraint stress. Conclusion and Implications: Overall, our findings provide evidence that IC glutamatergic signalling, acting via NMDA receptors, plays a prominent role in the control of autonomic and cardiovascular responses to restraint stress but does not affect neuroendocrine adjustments.

Background: Medulloblastoma is the most common malignant brain tumor in children. We aim to determine the survival in children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 to 2013 in Peru, a low-middle income country at the time of this analysis. We also describe the barriers and factors influencing outcomes. Methods: Between 1997-2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Two groups of treatment were identified 1997 – 2008 and 2009 – 2013. Event-free (EFS) and overall survival (OS) were obtained using Kaplan-Meier method and prognostic factors by univariate analysis (log-rank test). A survey was created to identify factors that may have influenced outcome. Results: Eighty-nine patients were included; median age was 8.1 years (range: 2.9-13.9 years). Surgical resection was complete in 39 patients. The five-year OS was 63% (95% CI: 53 – 74%) while EFS was 59% (95% CI: 49 – 71%). The variables adversely affecting survival were: anaplastic histology [compared to desmoplastic; OS: HR=3.5, p=0.03; EFS: HR=3.4, p=0.03], metastasis [OS: HR=3.4, p=0.01; EFS: HR=4.4, p=0.003], and treatment post-2008 [OS: HR=2.5, p=0.01; EFS: HR=2.5; p=0.01]. Conclusions: Outcomes for Medulloblastoma at INEN are low compared with high- income countries (HIC). Univariate analysis demonstrated that histological sub-type, metastasis at diagnosis, and treatment post-2008 all negatively affected outcomes in our study. The importance of multidisciplinary teamwork in the care of children with pediatric brain tumors as well as partnerships with loco-regional groups and colleagues in HIC is vastly beneficial.

Background. The treatment of childhood acute lymphoblastic leukemia (ALL) remains challenging in low-income countries. Here we evaluate the experience with a modified Berlin-Frankfurt-Münster (BFM) treatment protocol ALL-Moscow Berlin (MB)-91 at the Kantha Bopha hospitals, a charity-funded institution providing free pediatric care in Cambodia. Methods. This is a retrospective study including 110 unselected patients aged 9 months to 14 years diagnosed with ALL between 2015 and 2017. Patients were stratified in high- (HR) and standard-risk (SR) groups based on clinical criteria. The cumulative doses of anthracyclines were reduced to 120 mg/m2 for SR patients and consolidation was based on Capizzi methotrexate elements instead of cyclophosphamide, cytarabine and high dose methotrexate. Supportive empiric antibiotic treatment and whole blood transfusions were possible. Results. 63 patients (57 %) were HR, mostly based on high leukemia burden with hyperleukocytosis > 50 G/l, massive lymph node and hepato-splenic involvement, reflecting a high disease burden. 72 patients (65.5%) reached complete remission (CR) on day 36. The estimated 3-year overall survival (OS) was 34.9 %, 50.5 % for SR and 23.4 % for HR patients. Most events were due to severe infections (40 (53.3 %)) and bleeding (15 (20 %)), mostly during induction and consolidation. Relapse was confirmed in 13 cases (11.8 %). No patients abandoned treatment. Conclusion. ALL chemotherapy is feasible in a charity-funded public institution with results comparable to other low-middle income countries, but treatment-related mortality remains limiting. This will justify investments in diagnostics to stratify more patients for reduced intensity treatment and in supportive care.

This study compares the U.S. National Water Model (NWM) reanalysis snow outputs to observed snow water equivalent (SWE) and snow-covered area fraction (SCAF) at SNOTEL sites across the Western U.S. SWE was obtained from SNOTEL sites, while SCAF was obtained from MODIS observations at a nominal 500 m grid scale. Retrospective NWM results were at a 1000 m grid scale. We compared results for SNOTEL sites to gridded NWM and MODIS outputs for the grid cells encompassing each SNOTEL site. Differences between modeled and observed SWE were attributed to both model errors, as well as errors in inputs, notably precipitation and temperature. The NWM generally under-predicted SWE, partly due to precipitation input differences. There was also a slight general bias for model input temperature to be cooler than observed, counter to the direction expected to lead to under-modeling of SWE. There was also under-modeling of SWE for a subset of sites where precipitation inputs were good. Furthermore, the NWM generally tends to melt snow early. There was considerable variability between modeled and observed SCAF as well as the binary comparison of snow cover presence that hampered useful interpretation of SCAF comparisons. This is in part due to the shortcomings associated with both model SCAF parameterization and MODIS observations, particularly in vegetated regions. However, when SCAF was aggregated across all sites and years, modeled SCAF tended to be more than observed using MODIS. These differences are regional with generally better SWE and SCAF results in the Central Basin and Range and differences tending to become larger the further away regions are from this region. These findings identify areas where predictions from the NWM involving snow may be better or worse, and suggest opportunities for research directed towards model improvements.

Background. Whether small airway dysfunction (SAD), which is prevalent in asthma, helps to characterize wheezing phenotypes is undetermined. The objective was to assess whether SAD parameters obtained from impedance measurement and asthma probability are linked. Methods. One hundred and thirty-nine preschool children (mean age 4.7 years, 68% boys) suffering from recurrent wheeze underwent impulse oscillometry that allowed calculating peripheral resistance and compliance of the respiratory system (markers of SAD) using the extended RIC model (central and peripheral Resistance, Inertance and peripheral Compliance of the respiratory system). Children were classified using the probability-based approach of GINA guidelines (few, some, most having asthma). A principal component analysis (PCA) that determined the dimensions of wheezing disease evaluated the links between SAD and asthma probability. Results. Forty-seven children belonged to the few, 28 to the some and 64 to the most having asthma groups. Whereas their anthropometrics and measured parameters were similar, the most having asthma group exhibited the lowest mean value of airway inertance after bronchodilator probably due to airway inhomogeneities. PCA characterized nine independent dimensions including a peripheral resistance (constituted by baseline peripheral resistance, AX, R5-20Hz, X5Hz), a central resistance (baseline central resistance, R20Hz) and an airway size dimension (post-bronchodilator inertance and central resistance). PCA showed that the SAD markers were independent from clinical dimensions (control and asthma probability were two other dimensions) and did not help to define wheezing phenotypes. Conclusions. Lung function parameters obtained from impulse oscillometry and asthma probability were belonging to independent dimensions of the wheezing disease.

Geographic parthenogenesis (GP), a phenomenon where parthenogens and their close sexual relatives inhabit distinct geographic areas, has been considered an interesting topic to understand the adaptation to marginal habitats and the role of hybridization in evolution. Reports of GP from land and freshwater are numerous, however, this occurrence has been rarely reported on from the sea. Brown algae are mostly marine and are thought to include numerous obligate parthenogens; still, little is known about the distribution, origin, and evolution of parthenogens in this group. Here we report a novel pattern of GP in the isogamous brown alga Scytosiphon lomentaria. Sex ratio investigation demonstrated that, in Japan, sexual populations grew in the coast along warm ocean currents, whereas female-dominant parthenogenetic populations grew mainly in the coast along a cold ocean current. In the two localities where sexual and parthenogenetic populations were parapatric, parthenogens grew in more wave-exposed areas than sexuals. Population genetic and phylogenetic analyses, including those based on genome-wide single nucleotide polymorphism data, suggested that: (1) parthenogens evolved at least twice in S. lomentaria, (2) parthenogens did not originate from inter-species hybridization, (3) new parthenogenetic lineages have arisen from hybridizations between parthenogens and sexuals, and (4) parthenogens have a wider distribution than sexuals. We also showed that the production of sex pheromones, which attract male gametes, has been independently suppressed/lost in two parthenogenetic lineages. This parallel suppression/loss of the sexual trait may represent the direct origin of parthenogens, or the regressive evolution of a useless trait under asexuality.

Background: Transvenous implantable cardiac defibrillators (TV ICD) provide life-saving therapy for millions of patients worldwide. However, they are susceptible to several potential short- and long- term complications including cardiac perforation and pneumothorax, lead dislodgement, venous obstruction, and infection. The extravascular ICD (EV ICD) system’s novel design and substernal implant approach avoids the risks associated with TV ICDs while still providing pacing features and similar generator size to TV ICDs. Study Design: The EV ICD pivotal study is a prospective, multi-center, single-arm, non-randomized, pre-market clinical study designed to examine the safety and acute efficacy of the system. This study will enroll up to 400 patients with a Class I or IIa indication for implantation of an ICD. Implanted subjects will be followed up to approximately 3.5 years, depending on when the patient is enrolled. Objective: The clinical trial is designed to demonstrate safety and effectiveness of the EV ICD system in human use. The safety endpoint is freedom from major complications, while the efficacy endpoint is defibrillation success. Both endpoints will be assessed against prespecified criteria. Additionally, this study will evaluate antitachycardia pacing (ATP) performance, electrical performance, extracardiac pacing sensation, asystole pacing, appropriate and inappropriate shocks, as well as a summary of adverse events. Conclusion: The EV ICD pivotal study is designed to provide clear evidence addressing the safety and efficacy performance of the EV ICD System.

Enzymatic detachment of cells might damage important features of cells and could affect subsequent function of cells in various applications. Therefore, non-enzymatic cell detachment using thermosensitive polymer matrix is necessary for maintaining cell quality after harvesting. In this study, we synthesized thermosensitive PNIPAm-co-AAc-b-PS and PNIPAm-co-AAm-b-PS copolymers and LCST was tuned near to body temperature. Then, polymer solutions (5% w/v, 10% w/v, and 20% w/v) were spin coated to prepare films for cell adhesion and thermal-induced cell detachment. The apha-step analysis and SEM image of the films suggested that the thickness of the films depends on the molecular weight and concentration which ranged from 206 nm to 1330 nm for PNIPAm-co-AAc-b-PS and 97.5 nm to 497 nm for PNIPAm-co-AAm-b-PS. The contact angles of the films verified that the polymer surface was moderately hydrophilic at 37°C. From cell attachment and detachment studies, RAW264.7 cells, were convincingly proliferated on the films to a confluent of >80 % within 48 days. However, relatively more cells were grown on PNIPAm-co-AAm-b-PS (5%w/v) films and thermal-induced cell detachment was more abundant in this formulation. As a result, commercial cytodex 3 microcarrier was coated with PNIPAm-co-AAm-b-PS (5%w/v) and interestingly enhanced cell detachment with preserved potential of recovery was observed at low temperature during 3D culturing. Thus, surface modification of microcarriers with PNIPAm-co-AAm-b-PS could be vital strategy for non-enzymatic cell dissociation and able to achieve adequate number of cells with maximum cell viability, and functionality for various cell-based applications. Keywords: surface coated microcarriers; thermosensitive polymer; non-enzymatic cell detachment

Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly across the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralising antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4+ T cells, we were able to confirm a set of 9 immunodominant epitopes and characterise T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, by using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4+ T cell therapy of COVID-19.

Remote communication in ENT has been expanding, spurred by the COVID-19 pandemic. Conferences and teaching have moved online, enabling easier participation, and reducing financial and environmental costs. Online multi-disciplinary meetings have recently been instigated in Africa to discuss management of cases in head and neck cancer, or cochlear implantation, expanding access and enhancing patient care. Remote patient consultation has also seen an explosion, but existing literature suggests some caution, particularly because many patients in ENT need an examination to enable definitive diagnosis. Ongoing experience and more research is needed to better understand how remote communication will fit into our future working lives, both during and after the pandemic.

Postoperative UTI Postoperative UTI p Yes (n=20) No (n=269) Age (years) Ave 47.8± 12.6 47.9± 14.7 0,988‡ Sex Male Female 9 (%45) 11 (%55) 162 (%60.2) 107 (%39.8) 0.181† BMI Med 26.3± 3.2 27.4± 4.7 0.436§ DM Yes No 3 (%15) 17 (%85) 57 (%21.1) 212 (%78.9) 0.510† HT Yes No 4 (%20) 16 (%80) 69 (%25.6) 200 (%74.4) 0.575† Charlson Comorbidity İndex 0-1 ≥2 14 (%70) 6 (%30) 202 (%77.9) 57 (%22.1) 0.410† Stone Diameter(mm) Med 13.5± 4.1 15± 3.6 0.285§ Stone Localisation Upper Calyx Middle Calyx Lower Calyx Renal Pelvis Proximal Ureter Multipl 3 (%15) 2 (%10) 4 (%20) 8 (%40) 0 (%0) 3 (%15) 9 (%3.3) 29 (%10.8) 90 (%33.4) 72 (%26.8) 12 (%4.5) 67 (%24.9) 0.090† Preoperative Hydronephrosis Yes No 8 (%40) 12 (%60) 140 (%52.1) 128 (%47.9) 0.550† UTI History Yes No 11 (%55) 9 (%45) 55 (%20.5) 214 (%79.5) 0.000† Preoperative Dj Stent Yes No 8 (%40) 12 (%60) 63 (%23.4) 206 (%76.6) 0.097† Access Sheat Use Yes No 10 (%50) 10 (%50) 157 (%58.4) 112 (%41.6) 0.465† Operation time (min) Med 62.5± 16.6 60± 19.4 0.008§ Residual fragment Yes No 3 (%30) 17 (%70) 93 (%34.6) 176 (%65.4) 0.073†

The link between COPD and osteoporosis is unclear and yet to be understood. This study aimed at detecting the prevalence and investigate the predictors for low bone mineral density among COPD patients and tested a new risk assessment tool for the early screening of osteoporosis among COPD patients.This study is a longitudinal observational study conducted from June-2019 until December-2020 at a tertiary care setting in Penang, Malaysia. Follow-ups were arranged every six months. During the study, patients’ BMD was checked every visit, and the subjects’ pulmonary parameters were recorded, including; mMRC dyspnea scores, CAT scores, spirometry results, exacerbations history, and SpO2%. Furthermore, a novel risk assessment tool was validated in this study, and logistic regression was conducted to find low BMD predictors among COPD patients. Based on T-score, more than 50% of subjects were osteoporotic based. The overall mean±SD for patients’ age was 65.4±10.04. The overall mean±SD for patients’ BMI was 23.32±5.43. Both FEV1% predicted, and FEV/FVC was significantly lower among osteoporotic subjects, and lower mMRC stages were observed among non-osteoporotic patients. For the novel risk assessment tool, a cutoff point of 34 made the optimum balance between sensitivity and specificity (0.867 and 0.087, respectively) with an AUC of 0.934. Furthermore, severe COPD patients were four times at higher risk of getting osteoporosis, FEV% predicted, and FEV/FVC was inversely related to the risk of osteoporosis. Patients with severe dyspnea had twice the risk of getting osteoporosis.Osteoporosis was prevalent among COPD patients. For a screening tool, the risk assessment tool showed good sensitivity and precision in detecting osteoporotic subjects among COPD patients. Severe COPD patients were significantly at higher risk of getting osteoporosis.

Objective: Muscular dystrophies refers to a group of primary inherited myopathies that exhibit a chronic and unremitting progressive course. Quality of life is a concept, which mainly reflects individual responses given by a person to the physical, psychological, social and environmental impacts of the disease. In this study we aimed to evaluate quality of life and sociodemographic features of 146 patients who presented to the physical therapy and rehabilitation neuromuscular diseases outpatient clinic of our hospital. Methods: Patients’ sociodemographic data including gender, marital status and educational level were recorded and analyzed. WHOQOL-BREF survey was performed in order to determine quality of life in patients with muscular dystrophy. The scores obtained from the survey were transformed into WHOQOL 4-20 and WHOQOL 0-100 score ranges, and relationships between the sociodemographic data of the patients and WHOQOL-BRIEF survey results were evaluated. Results: Eighty-five (58.2%) patients were male and 61 (41.8%) were female. No statistically significant difference was found between the male and female MD patients in terms of the physical, psychological, social relationships and environmental domains of WHOQOL-BREF scale (for all p>0.05). No significant difference was found between single, married, divorced and widowed patients (for all p>0.05). There were significant differences between educational levels of the patients in terms of the mean WHOQOL-BREF scores (p<0.05). The mean scores increased as educational levels increased. Conclusion: Quality of life increases with the levels of education and does not differ according to gender and marital status in patients with muscular dystrophy. Patients with muscular dystrophy should be encouraged for education from the pediatric period.

A document by Dr. Okafor Miracle Uzochukwu. Click on the document to view its contents.

Population bottlenecks associated with founder events strongly impact the establishment and genetic makeup of populations. In addition to their genotype, founding individuals also bring along symbionts that can manipulate the phenotype of their host, affecting the host population establishment, dynamics and evolution. Thus, to understand introduction, invasion, and spread, we should identify the roles played by accompanying symbionts. In 1991, the parasitoid wasp, Hyposoter horticola, and its associated hyperparasitoid were accidentally introduced from the main Åland islands, Finland, to an isolated island in the archipelago, along with their host, the Glanville fritillary butterfly. Though the receiving island was unoccupied, the butterfly was present on some of the small islands in the vicinity. The three species have persisted as small populations ever since. A strain of the endosymbiotic bacterium Wolbachia has an intermediate prevalence in the H. horticola across the main Åland population. The infection increases susceptibility of the parasitoid to hyperparasitism. We investigated the establishment and spread of the parasitoid, along with patterns of prevalence of its symbiont using 323 specimens collected between 1992 and 2013, from five localities across Åland, including the source and introduced populations. Using 14 microsatellites and one mitochondrial marker, we suggest that the relatively diverse founding population and occasional migration between islands might have facilitated the persistence of all isolated populations, despite multiple local population crashes. We also show local near-fixation of Wolbachia, where the hyperparasitoid is absent, and selection against infected wasp genotypes is relaxed.

5 succinct/key points 1. There is a considerable burden to outpatient head and neck cancer (HaNC) surveillance, and it is unclear to what extent the current recommendations facilitate the detection of HaNC. 2. Our 100 patient retrospective analysis demonstrated three asymptomatic recurrences (all within the first year of follow up) and 20 symptomatic recurrences (mean time to recurrence of 21.4 months). 3. Seventy-four percent of those patients who recurred did so within the first two years following primary treatment, increasing up to 83% by three years. 4. We believe the value of routine follow up is more apparent within the first two to three years following primary treatment as this is when the rate of recurrence is highest. 5. We anticipate larger trials investigating the efficacy of an initial two years of frequent follow up followed by longer-term patient-led follow up.

COI-based DNA barcoding could be an efficient tool for species identification of deep-sea fishes and could lead to the discovery of cryptic species diversity. However, the availability of reference sequences of deep-sea fishes for DNA barcoding is limited, especially for fishes in the northwestern Pacific Ocean. In this study, we performed DNA barcoding of mesopelagic and demersal fish species on the continental shelf and upper slope, collected from deepwater fisheries around Japan and southern Taiwan, to accumulate the reference sequences of deep-sea fishes in the northwestern Pacific Ocean. Overall, we obtained the COI sequences of 123 species from 50 families. Genetic diversity within each species for which COI sequences were obtained from multiple specimens was examined, and we found that Chimaera phantasma (Chimaeridae), Harpadon microchir (Synodontidae), and Pyramodon ventralis (Carapidae) showed high intraspecific genetic differentiation of more than 2% Kimura two-parameter distance. Moreover, for 19 widespread deep-sea fishes, a comparison between our data and previously acquired COI sequence data suggested a high level (more than 2% Kimura two-parameter distance) of genetic differentiation between the northwestern Pacific Ocean and other oceans in each widespread species. These results suggest that many cryptic species or regional populations have not yet been discovered in deep-sea fishes. Alternatively, genetic differentiation was not found worldwide for six species. These results indicate that many taxonomic and biogeographical issues remain for deep-sea fishes, and our DNA barcoding data would provide better understanding of these issues.

BACKGROUND: Antibiotic therapy is essential for the treatment of cystic fibrosis (CF) lung infections. CF-specific airway pathophysiology and frequent antimicrobial exposure increase the risk of resistant infections, creating challenges to antibiotic selection. Antibiotic selection is generally based on previous cultures or hospital-wide antibiograms (HWA); however, most HWA exclude CF isolates. We developed a multi-year CF antibiogram (CFA) to compare with HWA and inform antibiotic selection. METHODS: CF culture data were collected 2015 - 2019 at a single pediatric CF center. All sputum and oropharyngeal swab isolates are included in the CFA. Demographics, microorganism isolates, and susceptibility information are presented. Susceptibilities were reported for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PA), Achromobacter species, Burkholderia species and Stenotrophomonas maltophilia. RESULTS: Over five years, the proportion of all SA isolates having methicillin-resistance was higher in the HWA (32%) than the CFA (28%). The most common gram-negative CF isolate was PA. Both gram-positive and gram-negative microorganisms were less susceptible in the CFA versus the HWA. CF isolates from sputum were less susceptible than oropharyngeal. MSSA and MRSA had significantly lower clindamycin susceptibility in the CFA compared to the HWA (MSSA 71% vs 79%, p<0.0001 and MRSA 39% vs 83%, p<0.0001). For every antimicrobial tested, PA isolates were less susceptible in the CFA compared to the HWA. There did not appear to be significant changes in susceptibility of CF isolates over time. CONCLUSIONS: These findings have clinical implications for empiric antimicrobial selection. A CFA will allow monitoring of resistance over time.

Anti-CD20 therapies in multiple sclerosis (MS) have become central to management of the disease since their FDA approval in 2017. As their role in MS management continues to grow, it is also increasingly important to know how such drugs can be better administered using current knowledge of how B cells repopulate after their depletion. To this end, individualizing therapy needs to be prioritized since a timed-dosing interval is perhaps not required based on evidence and it certainly unwelcome from a financial perspective.

CFTR (cystic fibrosis transmembrane conductance regulator) modulators are small molecules that directly change the CFTR protein, improving function of the CFTR chloride channel. Beginning in 2012 with the FDA approval of the first CFTR modulator, ivacaftor, this class of medication has had largely positive effects on many outcomes in people with cystic fibrosis (pwCF), including lung function, quality of life, and growth. There have been continued exciting developments in the current research on CFTR modulators, expanding beyond original studies. This first part of a three-part Cystic Fibrosis (CF) Year in Review 2020 will focus on research on CFTR modulators. Subsequent parts of the CF year in review will cover pulmonary and infectious inflammatory aspects, and the multisystem effects of CF in the 2020 literature. The review focuses on articles from Pediatric Pulmonology, but it includes articles from other journals that are of particular interest to clinicians. New developments in CF research continue to be brought forth to the CF community, deepening the understanding of this disease and improving clinical care.